PCSK9 immunization using nanoliposomes: preventive efficacy against hypercholesterolemia and atherosclerosis.
PCSK9
atherosclerosis
dyslipidemia
immunization
Journal
Archives of medical science : AMS
ISSN: 1734-1922
Titre abrégé: Arch Med Sci
Pays: Poland
ID NLM: 101258257
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
02
2021
accepted:
02
03
2021
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
16
9
2021
Statut:
epublish
Résumé
The aim of the study was to study a nanoliposomal anti-PCSK9 vaccine as a novel approach for cholesterol lowering via PCSK9 inhibition. An immunogenic peptide construct termed immunogenic fused PCSK9-tetanus (IFPT) was displayed on the surface of liposome nanoparticles (L-IFPT) and mixed into alum adjuvant (L-IFPTA+). The manufactured vaccine formulations IFPT, L-IFPT, L-IFPTA+, IFPTA+, and free nanoliposomes were subcutaneously injected four times with bi-weekly intervals in C57BL/6 mice on a severe atherogenic protocol. Among the formulations, L-IFPTA+ vaccine was found to elicit the highest IgG response against PCSK9 peptide. The induced PCSK9 antibodies inhibited PCSK9-LDLR interaction through binding to PCSK9 in vaccinated mice. Liver low-density lipoprotein receptor (LDLR) protein was increased in vaccinated mice. L-IFPTA+, L-IFPT and IFPTA+ vaccines reduced total cholesterol by up to -38.13 ±3.8% ( L-IFPTA+ vaccine can induce long-lasting, functional and safe PCSK9-specific antibodies in hypercholesterolemic C57BL/6 mice, providing a long-term protective impact on dyslipidemia and atherosclerosis.
Identifiants
pubmed: 34522266
doi: 10.5114/aoms/133885
pii: 133885
pmc: PMC8425258
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1365-1377Informations de copyright
Copyright: © 2021 Termedia & Banach.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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